Briefings in Functional Genomics and Proteomics Advance Access published online on February 23, 2006
Briefings in Functional Genomics and Proteomics, doi:10.1093/bfgp/ell003
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* To whom correspondence should be addressed. The conventional string-based bioinformatic methods of genomic sequence analysis are often insufficient to identify DNA regulatory elements, since many of these do not have a recognizable motif. Even in case a sequence pattern is known to be associated with an element it may only partially mediate its function. This suggests that properties not correlated with the details of base sequence contribute to regulation. One of these attributes is the DNA strand-separation potential, known as SIDD (stress-induced duplex destabilization) which facilitates the access of tracking proteins and the formation of local secondary structures. Using the type 1 interferon gene cluster as a paradigm, we demonstrate that the imprints in a SIDD profile coincide with chromatin domain borders and with DNAse I hypersensitive sites to which regulatory potential could be assigned. The approach permits the computer-guided identification of yet unknown, mostly remote sites and the design of artificial elements with predictable properties for multiple applications. Silke Winkelmann is a PhD student in the group of JBO where she develops novel methods to study transcriptional properties as they relate to nuclear structure. Martin Klar received his PhD and a subsequent prize in 2005 for his work in the same group dealing with the remote control of the human and mouse interferon-beta genes. He could verify the major predictions of SIDD profiles. http://opus.tu-bs.de/opus/volltexte/2005/713/pdf/DissMK.pdf Craig Benham is the senior biomathematical counterpart of the group. He has an AB degree from Swartmore College and a PhD in Mathematics from Princeton University. His studies of biopolymer structure started when he worked with John Kozak at the University structure (proteins) and during his postdoctoral years with Max Delbrueck at Cal Tech. After leading the Department of Biomathematics at Mount Sinai, NY, he became a founding Associate Director of the UC Davis Genome Center. Contacts to the Braunschweig group date back to 1994, the first joint publication to 1997. Prashanth AK joined Craig Benham at Mount Sinai and now he shares his research programmes at Davis. Nowadays he is the active cooperation partner of the Braunschweig people. Sandra Goetze did her PhD in the lab of Prof. Bode (1998-2001) working on the identification and biochemical analysis of boundary elements under consideration of biomathematical models. Currently she is investigating the three-dimensional chromatin organization in the human interphase nucleus in the context of an FP6 European Program in the lab of Prof. van Driel in Amsterdam. http://opus.tu-bs.de/opus/volltexte/2004/587/pdf/Dissertation.pdf Angela Gluch (born Knopp) initiated participation in the human genome project together with JBO. The major concepts realized in the present contribution go back to her initiative. She received PhD in 2001. She may return to the group after maternity leave in 2006. http://opus.tu-bs.de/opus/volltexte/2001/200/pdf/Dissertati.pdf Juergen Bode studied Organic Chemistry at the Technical University of Braunschweig. His switch to Biochemistry occurred during postdoctoral years at the California Institute of Technology (CalTech; enzyme and neuroreceptor structures with Michael A. Raftery) and University of Oregon, Eugene (UofO; enzyme kinetics with Sidney A. Bernhard). The final direction of research initiated in the year the nucleosome was discovered. It widened to aspects of nuclear structure as these relate to gene expression. He is a group leader (Epigenetics) at GBF (German Research Center of Biotechnology at Braunschweig) and a Professor of Biochemistry at the Technical University (http://juergenbode.de.vu; http://cvjbo.de.vu).
Paper
The positive aspects of stress: strain initiates domain decondensation (SIDD)
Silke Winkelmann,
Martin Klar,
Craig Benham,
Prashanth AK,
Sandra Goetze,
Angela Gluch,
and
Juergen Bode *
Juergen Bode, E-mail: jbo{at}gbf.de
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